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Chronic Fatigue Syndrome: Differential Diagnoses & Workup

Author: Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Contributor Information and Disclosures

Updated: Oct 19, 2009

Differential Diagnoses

Fibromyalgia
Hypothyroidism
Lyme Disease

Other Problems to Be Considered

Chronic fatigue syndrome (CFS) must be differentiated from other disorders that have a fatigue component. CFS is typically easy to differentiate from other causes of CFS based on the presence of cognitive dysfunction, which is absent in almost all other fatigue-producing disorders. Possible differential diagnoses include the following:

  • Adrenal insufficiency
  • Malignancy
  • AIDS
  • Liver disease
  • Renal disease

Psychosomatic illness: Patients with psychosomatic disorders may have elevated IgG VCA EBV titers, which may be mistakenly taken as evidence for CFS. As mentioned above, EBV infection may precede CFS but does not cause CFS. Such patients do not present with the physical findings or abnormal laboratory findings that characterize CFS. Such patients also lack the cognitive dysfunction characteristic of CFS.

Lyme disease: CFS is readily differentiated from Lyme disease in various ways. Patients from areas with endemic Lyme disease may have elevated IgG Lyme titers. Few of these patients have neuroborreliosis, which is diagnosed based on measuring cerebrospinal fluid (CSF) and serum IgM and IgG Lyme titers simultaneously. CSF titers that are higher than serum titers indicate neuroborreliosis. Acute Lyme disease usually has a neurologic component, but chronic neuroborreliosis is distinctly uncommon. Patients with chronic neuroborreliosis do not have the same cognitive defects as patients with CFS (see History) and usually lack fatigue.

Fibromyalgia: Fibromyalgia does not cause cognitive defects, so it is readily differentiated from CFS. Furthermore, patients with CFS do not have trigger points, which are characteristic of fibromyalgia.

Other diseases may be ruled out based on history, physical, and/or laboratory findings.

Workup

Laboratory Studies

Laboratory tests have two functions in chronic fatigue syndrome (CFS). First, tests are used to exclude other fatigue-causing diseases, and, second, they may be helpful diagnosing CFS.

  • The most consistent laboratory abnormality in patients with CFS is an extremely low erythrocyte sedimentation rate (ESR), which approaches zero. Typically, patients with CFS have an ESR of 0-3 mm/h. An normal ESR or one that is in the upper reference range suggests another diagnosis.
  • Thyroid, adrenal, and liver function tests are useful in excluding disorders that may have a fatigue component.
  • Most patients with CFS usually have 2 or 3 of the following abnormalities:
    • Elevated IgM/IgG coxsackievirus B titer
    • Elevated IgM/IgG HHV-6 titer
    • Elevated IgM/IgG C pneumoniae titer
    • Decreased NK cells, either the percentage or their activity
  • CFS laboratory abnormalities are not specific, but, taken together, the abnormalities provide a pattern of consistency with CFS in patients who have a cognitive dysfunction in whom other diseases have been excluded as a cause for their fatigue.
  • The WBC count in patients with CFS is normal. Leukopenia, leukocytosis, or an abnormal cell differential count indicates a diagnosis other than CFS, and another cause should be pursued to explain these findings.
  • Results of liver function tests are within the reference range in patients with CFS.
  • Increased levels of serum transaminases, alkaline phosphatase, or lactic dehydrogenase should prompt a search for another explanation because these values are typically normal CFS.
  • Serum protein electrophoresis is normal in patients with CFS but may be used to rule out other diseases that cause fatigue, including lymphoma and myeloma.
  • Urinalysis findings are unremarkable in CFS.

Imaging Studies

  • CT scanning or MRI of the brain is useful to rule out CNS disorders in patients with otherwise unexplained CNS symptomatology. Results of CT scans and MRI may be normal in patients with CFS.
  • Findings of CNS imaging studies are not specific for CFS and are thus used to rule out alternative explanations rather than to diagnose CFS.
  • Positron emission tomography (PET) scans show hypoperfusion in the frontoparietal/temporal region.

Other Tests

  • Tilt-table testing became popular after a study showed that one of two large population groups with CFS had a minimal degree of relative adrenal insufficiency. The study showed that the groups could be differentiated as large groups but that the overlap was such that, in the individual case, tilt-table testing was not helpful. This author has not found a tilt-table test useful and has recommended that practitioners abandon this practice because, in some patients, the test has precipitated cardiovascular problems and has questionable diagnostic utility.
  • Extensive immunological testing is not indicated in patients with CFS because it is neither diagnostic nor specific for CFS. Similarly, RBC magnesium levels and allergy testing, particularly serological tests for Candida, are of no value.

More on Chronic Fatigue Syndrome

Overview: Chronic Fatigue Syndrome
Differential Diagnoses & Workup: Chronic Fatigue Syndrome
Treatment & Medication: Chronic Fatigue Syndrome
Follow-up: Chronic Fatigue Syndrome
References
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Further Reading

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Keywords

chronic fatigue syndrome, encephalomyalgia, CFS, myalgic encephalomyelitis, fatigue, chronic fatigue, idiopathic fatigue, viral infection, Chlamydia pneumoniae, C pneumoniae, Epstein-Barr virus, EBV infection

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Contributor Information and Disclosures

Author

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Wesley W Emmons, MD, FACP, Assistant Professor, Department of Medicine, Thomas Jefferson University; Consulting Staff, Infectious Diseases Section, Department of Internal Medicine, Christiana Care, Newark, DE
Wesley W Emmons, MD, FACP is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and International AIDS Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Thomas M Kerkering, MD, Chief of Infectious Diseases, Virginia Tech, Carilion School of Medicine, Roanoke, Virginia
Thomas M Kerkering, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Public Health Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Medical Society of Virginia, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD, Professor, Stewart G Wolf Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Association of Professors of Medicine, Association of Program Directors in Internal Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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